Research Project 3: The impact of inhaled environmental exposures on the microbiota of the upper airways of African children: Abstract Inhaled exposures, such as environmental tobacco smoke (ETS), volatile compounds, particulate matter and microbial components modify the risk of developing respiratory tract illness in children, including asthma and lower respiratory tract infection (LRTI). Exposure to high levels of inhaled pollutants is common in our cohort of South African children. These inhaled exposures may also affect the microbial composition of the airways, which may, in part, mediate the effect on respiratory illness. In the sub-Sahelian region of Africa, during the dry season, there are outbreaks of meningococcal disease, which are preceded by oropharyngeal colonization with Neisseria meningitidis. We therefore propose to study (1) the association between indoor air pollutants and the upper airway microbiota, including NP carriage of S. pneumoniae and oropharyngeal carriage of N. meningitidis; (2) the association between the household dust microbiota and the NP and OP microbiota; and (3) seasonal variation in inhaled exposures and the relationship with the NP and OP microbiota. We will utilize existing NP and household dust specimens, and detailed data on inhaled pollutants and ETS exposure from our cohort in South Africa. We will also prospectively collect NP and OP samples from children within households in The Gambia, and measure particulate matter and ETS exposure. We will use amplicon sequencing to define the bacterial and fungal components of the NP, OP and household dust microbiota. We will do selective culture to identify NP colonization with S. pneumoniae and OP colonization with N. meningitidis. We will determine the association between exposure to inhaled pollutants and the NP/OP microbiota and between the household dust microbiota and the NP/OP microbiota. Description of the influence of inhaled environmental exposures on the NP and OP microbiota will contribute towards an improved understanding of risk factors that influence the upper airway microbiota. Together with work done on projects 1 and 2 this project will identify potentially modifiable exposures that contribute, through their effect on the NP or OP microbiota, to carriage of N. meningitidis or S. pneumoniae and to respiratory illness in children.